FKBP-12 Exhibits an Inhibitory Activity on Calcium Oxalate Crystal Growth in Vitro

Han, In Sook; Nakagawa, Yasushi; Park, Jong Wook; Suh, Min Ho; Suh, Sung Il; Shin, Song Woo; Ahn, Sungjin; Choe, B. K.

doi:10.3346/jkms.2002.17.1.41

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Several molecules are known to inhibit CaOx crystal formation in physiologic condition, including nephrocalcin, osteonectin, mannanbinding lectin-associated plasma protein, and FK506-binding protein, some of which are immunolocalized to renal proximal tubules. 8 It is possible that lower levels of these molecules may promote CaOx deposition. Although this hypothesis has not been tested, at least one of these molecules, ie, nephrocalcin, was identified in RCCs and shown to decrease in ESRDassociated RCCs.…”

Section: Discussionmentioning

confidence: 99%

Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease

Süle¹,

Yakupoglu²,

Shen³

et al. 2005

American Journal of Surgical Pathology

100

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The main complication of acquired cystic kidney disease (ACKD) is frequent development of renal tumors, including renal cell carcinoma (RCC). Intratumoral deposition of calcium oxalate (CaOx) is a distinct feature of ACKD-associated RCCs, but several features of this type of RCC are not known. Features of the 30 end-stage renal disease (ESRD)-associated RCCs identified within a 13-year period, including eight with CaOx deposition, were analyzed. Pathologic and clinical features of CaOx positive (+) and negative (-) RCCs were evaluated and compared. The CaOx+ RCCs showed higher tendency for bilaterality and multifocality. Seven tumors displayed distinctive morphologic features characterized by tumor cells with ill-defined cell membrane, abundant granular eosinophilic cytoplasm, large nuclei, and prominent nucleoli. One tumor was of clear cell type. Regardless of histologic type, all tumors displayed a proximal tubular differentiation. No significant difference was noted for tumors' stage, proliferation, and apoptosis rate between the CaOx+ and CaOx- RCCs. CaOx+ RCCs account for a significant portion of all ESRD-associated RCCs. The majority of these RCCs display a distinctive morphologic profile. Proximal tubular cell differentiation in conjunction with ESRD-mediated high serum level may be pathogenetically important for intratumoral CaOx deposition. These RCCs seems to have a relatively good prognosis.

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Section: Discussionmentioning

confidence: 99%

Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease

Süle¹,

Yakupoglu²,

Shen³

et al. 2005

American Journal of Surgical Pathology

100

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“…Interestingly, these stone inhibitors have similar physicochemical properties as they are small anionic proteins that can bind to calcium and inhibit either growth or aggregation of CaOx crystals. Only a few other proteins have been identified as inhibitors of stone formation [62][63][64].…”

Section: Proteomic Identification Of Novel Urinary Modulators Of Caoxmentioning

confidence: 99%

Proteomics and Kidney Stone Disease

Thongboonkerd

2008

Proteomics in Nephrology - Towards Clinical Applications

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Kidney stone disease (nephrolithiasis) is an ancient and common affliction. It has been recognized for a long time with evidence of stone found in approximately 7,000-year-old mummies and remains a common problem worldwide, indicating ineffective prevention in the past. Precise pathogenic and molecular mechanisms of kidney stone formation are still poorly understood and should be further elucidated. Also, identification of novel therapeutic targets for better therapeutic outcome and successful prevention of the occurrence and recurrence of the stone are crucially required. One of the most promising tools for current and future biomedical research is proteomics, which has been extensively and widely applied to the nephrology field during the past 5 years. Its high-throughput capability holds a great promise also to kidney stone research. This chapter provides a brief overview of proteomic methodologies recently used for the investigation of nephrolithiasis and recent proteomic studies of nephrolithiasis are summarized.

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“…Interestingly, these stone inhibitors have similar physical and chemical properties; they are small anionic proteins that bind to calcium and inhibit either growth or aggregation of CaOx crystals. Only a few additional proteins have been identified as inhibitors of stone formation (27)(28)(29). In the present study, we have purified and identified a novel CaOx crystal growth inhibitor, namely urinary trefoil factor 1 (TFF1), from normal human urine using conventional biochemical methods and recent advances in mass spectrometry (MS).…”

Section: Introductionmentioning

confidence: 99%

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Chutipongtanate

Nakagawa²,

Sritippayawan³

et al. 2005

Journal of Clinical Investigation

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Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5-to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.

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FKBP-12 Exhibits an Inhibitory Activity on Calcium Oxalate Crystal Growth in Vitro

Cited by 4 publications

References 25 publications

Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease

Calcium Oxalate Deposition in Renal Cell Carcinoma Associated With Acquired Cystic Kidney Disease

Proteomics and Kidney Stone Disease

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

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